Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: Mechanistic possibilities

AbstractGLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control.

Download Full-text

Abstract #295 GLP-1 Receptor Agonists and Death From Any Cause in Elderly Patients with Type 2 Diabetes Mellitus: A Post-Hoc Analysis

Endocrine Practice ◽

10.1016/s1530-891x(20)47140-x ◽

2018 ◽

Vol 24 ◽

pp. 80-81

Author(s):

Konstantinos Toulis ◽

Krishna Gokhale ◽

G. Neil Thomas ◽

Wasim Hanif ◽

Krishnarajah Nirantharakumar ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Elderly Patients ◽

Post Hoc Analysis ◽

Receptor Agonists ◽

Post Hoc

Download Full-text

TYPE 2 DIABETES MELLITUS REMISSION AND ITS PREDICTION AFTER TWO-STAGE SURGICAL TREATMENT OF PATIENTS WITH MORBID OBESITY

Wiadomości Lekarskie ◽

10.36740/wlek201905102 ◽

2019 ◽

Vol 72 (5) ◽

pp. 739-743

Author(s):

Oleksandr Yu. Ioffe ◽

Mykola S. Kryvopustov ◽

Yuri A. Dibrova ◽

Yuri P. Tsiura

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Morbid Obesity ◽

Weight Loss ◽

Type 2 Diabetes Mellitus ◽

Surgical Treatment ◽

Two Stage ◽

C Peptide ◽

Peptide Level

Introduction: Morbid obesity (MO) has a significant impact on mortality, health and quality of life of patients. Type 2 diabetes mellitus (T2DM) is a common comorbidity in patients with MO. The aim is to study T2DM remission and to develop a prediction model for T2DM remission after two-stage surgical treatment of patients with MO. Materials and methods: The study included 97 patients with MO. The mean BMI was 68.08 (95% CI: 66.45 - 69.71) kg/m2. 70 (72,2%) patients with MO were diagnosed with T2DM. The first stage of treatment for the main group (n=60) included the IGB placement, for the control group (n=37) - conservative therapy. In the second stage of treatment the patients underwent bariatric surgery. The study addresses such indicators as BMI, percentage of weight loss, percentage of excess weight loss, ASA physical status class, fasting glucose level, HbA1c, C-peptide. Results: Two-stage treatment of morbidly obese patients with T2DM promotes complete T2DM remission in 68.1% of patients. The risk prediction model for failure to achieve complete T2DM remission 12 months after LRYGB based on a baseline C-peptide level has a high predictive value, AUC = 0.84 (95% CI: 0.69-0.93), OR = 0.23 ( 95% CI: 0.08-0.67). Conclusions: Two-stage treatment of patients with MO promotes improvement of carbohydrate metabolism indicators. With a C-peptide level > 3.7 ng/ml, prediction of complete T2DM remission 12 months after Laparoscopic Roux-en-Y Gastric Bypass is favorable.

Download Full-text

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190828161409 ◽

2019 ◽

Vol 19 (20) ◽

pp. 1818-1849 ◽

Cited By ~ 4

Author(s):

Ban Liu ◽

Yuliang Wang ◽

Yangyang Zhang ◽

Biao Yan

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Dysfunction ◽

Sglt2 Inhibitors ◽

Sodium Glucose Cotransporter ◽

Glucose Reabsorption ◽

Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

Download Full-text